Department of Virology, Pasteur Institute of Iran, Tehran, Iran.
Department of Neurosurgery and Neurology, Westfälische Wilhelms-Universität Münster, Münster, Germany.
Nutr Cancer. 2022;74(1):372-382. doi: 10.1080/01635581.2020.1865419. Epub 2020 Dec 26.
We perceive the potential of combined immunotherapy for the synergistic treatment of human papillomavirus (HPV)-associated tumors. So, the tumor inhibiting effects of combination of TD2a and GM-CSF on the TC-1 growth were evaluated In Vivo using lymphocyte proliferation, lymphocyte cytotoxicity, splenocyte, and tumor cytokine assays. The results showed that tumor inhibition in transplanted mice in the GM-CSF combined with probiotic group was significantly higher than that observed in the other groups excluding GM-CSF group whose tumor inhibition effect was considerable. The findings also indicated that the combined group could generate tumor-specific cytolytic and splenocyte proliferative responses. The levels of IFN-γ, IL-4, and IL-12 after treating with GM-CSF combined with probiotic were significantly higher than those of other groups. The intratumoral Tumor Necrosis Factor Related Apoptosis-Inducing Ligand (TRAIL) was also significantly increased in the combined group. Tumor analysis further showed that the combined group decreased the accumulation of IL-10 in the tumor microenvironment of treated mice. Furthermore, tumor volume analysis demonstrated that combination group and even GM-CSF suppress tumor growth. Our findings showed that the combination of GM-CSF and probiotic results in improved tumor suppression against HPV-associated tumors and stimulates enhancement of specific antitumor immune responses.
我们发现联合免疫疗法在协同治疗人乳头瘤病毒(HPV)相关肿瘤方面具有潜力。因此,我们评估了 TD2a 和 GM-CSF 联合对 TC-1 生长的体内肿瘤抑制作用,使用淋巴细胞增殖、淋巴细胞细胞毒性、脾细胞和肿瘤细胞因子测定。结果表明,在 GM-CSF 联合益生菌组的移植小鼠中,肿瘤抑制作用明显高于其他组(GM-CSF 组除外,其肿瘤抑制作用相当可观)。研究结果还表明,联合组可产生肿瘤特异性细胞溶解和脾细胞增殖反应。用 GM-CSF 联合益生菌处理后,IFN-γ、IL-4 和 IL-12 的水平明显高于其他组。联合组肿瘤内肿瘤坏死因子相关凋亡诱导配体(TRAIL)也明显增加。肿瘤分析进一步表明,联合组减少了治疗小鼠肿瘤微环境中 IL-10 的积累。此外,肿瘤体积分析表明,联合组甚至 GM-CSF 可抑制肿瘤生长。我们的研究结果表明,GM-CSF 和益生菌的联合使用可改善对 HPV 相关肿瘤的肿瘤抑制作用,并刺激特异性抗肿瘤免疫反应的增强。